NUS researchers uncover a novel protein which drives cancer progression

June 29, 2020

Cancers arise when the genetic code of normal cells is altered, causing excessive growth. Researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS) have discovered a protein that drives the growth of cancers of the esophagus or liver by altering the genetic code in a novel way.

The protein, death associated protein 3 (DAP3), represses a process called adenosine-to-inosine (A-to-I) RNA editing that normally corrects the genetic code to ensure that genes are expressed correctly. By inhibiting RNA editing, DAP3 acts as an oncogene -- a gene that has the potential to cause cancer. This discovery offers the potential of developing novel drugs that target DAP3 for cancer treatment.

The study was led by Assistant Professor Polly Chen, a Principal Investigator at CSI Singapore, and the findings were published in the scientific journal Science Advances on 17 June 2020.

Understanding A-to-I RNA editing

RNAs are one of the most important classes of molecules in cells. They not only convert the genetic information stored in DNA to proteins, but also play critical regulatory roles in various biological processes. RNA editing is a process in which RNA is changed after it is made from DNA, resulting in an altered gene product. In humans, the most common type of RNA editing is A-to-I editing, which is mediated by ADAR proteins (ADAR1 and ADAR2). In the past decade, many studies have reported that the accumulation of deleterious changes in A-to-I RNA editing can trigger a cell to develop into cancer. However, the current knowledge of how the A-to-I RNA editing process is regulated in cancer is still limited.

The CSI Singapore research team therefore conducted a research study to understand how DAP3 -- the interacting protein of the A-to-I RNA editing catalytic enzymes (ADAR1 and ADAR2) -- regulates this process in cancer cells.

Promising drug target for cancer treatment

The team demonstrated that DAP3 could destroy the binding of ADAR2 protein to its target RNAs, thereby inhibiting the A-to-I RNA editing in cancer cells. This suppression is likely to be one of the pathways by which DAP3 could promote cancer development.

Their analysis also revealed that the expression of DAP3 is elevated in 17 types of cancer. Further experiments demonstrated that DAP3 acted as an oncogene in esophageal cancer and liver cancer cells. Interestingly, they also identified the gene PDZD7, one of DAP3-inhibited editing targets and discovered that altered editing of PDZD7 generated a new PDZD7 protein product which contributed to the DAP3-driven tumor growth.

Overall, these observations shed light on the complexity of the regulation of the A-to-I RNA editing process in cancer cells, and suggest that DAP3 could be a promising target for future cancer drug development.

"With this new knowledge, we can now look into how we can intervene in the interactions between DAP3 and ADAR proteins in order to interfere with cancer-promoting processes mediated by RNA editing in the cell," said research leader Asst Prof Chen.
-end-


National University of Singapore

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.